Psychoneuroimmunologic research proposed is addressed to an understanding of the regulation or modulation of immune responses by behavioral processes operating through the central nervous system and the endocrine system. It is based upon recent data on neuroendocrine factors in immunoregulation and upon our previous observations that humoral and cell-mediated immune responses are subject to behavioral conditioning. Using a taste aversion conditioning paradigm, rats and/or mice are conditioned by pairing a distinctively flavored drinking solution (the conditioned stimulus) with an immunomodulating agent (the unconditioned stimulus). After conditioning, all animals are subjected to immunogenic stimulation. In vitro and in vivo immunologic reactivity is measured in conditioned animals that are reexposed to the conditioned stimulus or those that receive no further stimulation -- and in nonconditioned and placebo treated groups. Proposed studies will clarify and extend previous observations by (1) introducing greater operational control over the conditioning paradigm, (2) investigating the experimental extinction of conditioned immune responses, (3) using antigenic stimuli as unconditioned stimuli, and (4) using flow cytometry to evaluate the effects of conditioning on subpopulations of lymphocytes. The biologic impact of behaviorally- induced alterations in immunologic reactivity will be assessed by studying the effects of conditioning processes on the development and course of spontaneously occurring autoimmune disease in (NZBxNZW)F1 and Mr1 mice. It is also proposed to initiate a program of developmental research in psychoneuroimmunology in which the effects of behavioral and neuroendocrine manipulations experienced during early life on adult immunocompetence will be determined. This integrative research program will be accomplished in an expanded interdisciplinary groups representing expertise in behavior, immunology, neuroendocrinology and neuroanatomy.